| First Author | Qian K | Year | 2023 |
| Journal | Nature | Volume | 613 |
| Issue | 7942 | Pages | 160-168 |
| PubMed ID | 36477540 | Mgi Jnum | J:333997 |
| Mgi Id | MGI:7444870 | Doi | 10.1038/s41586-022-05507-1 |
| Citation | Qian K, et al. (2023) CLSTN3beta enforces adipocyte multilocularity to facilitate lipid utilization. Nature 613(7942):160-168 |
| abstractText | Multilocular adipocytes are a hallmark of thermogenic adipose tissue(1,2), but the factors that enforce this cellular phenotype are largely unknown. Here, we show that an adipocyte-selective product of the Clstn3 locus (CLSTN3beta) present in only placental mammals facilitates the efficient use of stored triglyceride by limiting lipid droplet (LD) expansion. CLSTN3beta is an integral endoplasmic reticulum (ER) membrane protein that localizes to ER-LD contact sites through a conserved hairpin-like domain. Mice lacking CLSTN3beta have abnormal LD morphology and altered substrate use in brown adipose tissue, and are more susceptible to cold-induced hypothermia despite having no defect in adrenergic signalling. Conversely, forced expression of CLSTN3beta is sufficient to enforce a multilocular LD phenotype in cultured cells and adipose tissue. CLSTN3beta associates with cell death-inducing DFFA-like effector proteins and impairs their ability to transfer lipid between LDs, thereby restricting LD fusion and expansion. Functionally, increased LD surface area in CLSTN3beta-expressing adipocytes promotes engagement of the lipolytic machinery and facilitates fatty acid oxidation. In human fat, CLSTN3B is a selective marker of multilocular adipocytes. These findings define a molecular mechanism that regulates LD form and function to facilitate lipid utilization in thermogenic adipocytes. |
